Daniel A. N. Barbosa, M.D., is a Research Fellow working under the mentorship of Dr. Casey H. Halpern (Assistant Professor of Neurosurgery) and Dr. Jennifer McNab (Associate Professor of Radiology). He received his medical degree from the Federal University of the State of Rio de Janeiro in 2018. During his clinical education, Dr. Barbosa followed several renowned neurosurgeons and neurologists, and had a large experience with neurological and psychiatric patients. He developed great interest for the investigations of neurosurgical techniques to improve brain function. The invaluable experiences with these patients shaped a great interest on the investigations of neurosurgical techniques to improve brain function. His clinical and academic training together with the research experience provided him with an excellent background in multiple biological disciplines including neurosurgery, neurology, psychiatry, and neuroimaging. He also had the opportunity of joining a team of neurosurgeons and clinical scientists in the largest clinical study on deep brain stimulation for morbid obesity to date. With Drs. Ricardo de Oliveira-Souza, Alessandra Gorgulho, and Antônio De Salles (UCLA Emeritus Professor of Neurosurgery), Dr. Barbosa has led a systematic review on the topic. He also worked on the development and the publishing of this study protocol as well as that of a clinical trial of a novel neurosurgical therapy for depression. During his graduate career, these clinical investigations generated several peer-reviewed publications, book chapters, and conference presentations.
Now, his investigation is contributing to the ongoing first-in-human early feasibility trial of closed-loop neuromodulation of the nucleus accumbens for Loss of Control Eating. He is also working on the design of innovative, invasive clinical studies for conditions like Obsessive Compulsive Disorder. He is committed to investigate cutting-edge neuroimaging and neurophysiology modalities, including diffusion magnetic resonance imaging, as well as novel brain-clearing techniques to improve stereotactic targeting neuromodulation for pathological impulsivity, a pervasive symptom in a wide range of neurological and neuropsychiatric disorders.
M.D., Universidade Federal do Estado do Rio de Janeiro (2018)
Brain-Responsive Neurostimulation for Loss of Control Eating: Early Feasibility Study.
Loss of control (LOC) is a pervasive feature of binge eating, which contributes significantly to the growing epidemic of obesity; approximately 80 million US adults are obese. Brain-responsive neurostimulation guided by the delta band was previously found to block binge-eating behavior in mice. Following novel preclinical work and a human case study demonstrating an association between the delta band and reward anticipation, the US Food and Drug Administration approved an Investigational Device Exemption for a first-in-human study.To assess feasibility, safety, and nonfutility of brain-responsive neurostimulation for LOC eating in treatment-refractory obesity.This is a single-site, early feasibility study with a randomized, single-blinded, staggered-onset design. Six subjects will undergo bilateral brain-responsive neurostimulation of the nucleus accumbens for LOC eating using the RNS® System (NeuroPace Inc). Eligible participants must have treatment-refractory obesity with body mass index ≥ 45 kg/m2. Electrophysiological signals of LOC will be characterized using real-time recording capabilities coupled with synchronized video monitoring. Effects on other eating disorder pathology, mood, neuropsychological profile, metabolic syndrome, and nutrition will also be assessed.Safety/feasibility of brain-responsive neurostimulation of the nucleus accumbens will be examined. The primary success criterion is a decrease of ≥1 LOC eating episode/week based on a 28-d average in ≥50% of subjects after 6 mo of responsive neurostimulation.This study is the first to use brain-responsive neurostimulation for obesity; this approach represents a paradigm shift for intractable mental health disorders.
View details for DOI 10.1093/neuros/nyaa300
View details for PubMedID 32717033
An Open-Label Clinical Trial of Hypothalamic Deep Brain Stimulation for Human Morbid Obesity: BLESS Study Protocol.
Human morbid obesity is increasing worldwide in an alarming way. The hypothalamus is known to mediate its mechanisms. Deep brain stimulation (DBS) of the ventromedial hypothalamus (VMH) may be an alternative to treat patients refractory to standard medical and surgical therapies.To assess the safety, identify possible side effects, and to optimize stimulation parameters of continuous VMH-DBS. Additionally, this study aims to determine if continuous VMH-DBS will lead to weight loss by causing changes in body composition, basal metabolism, or food intake control.The BLESS study is a feasibility study, single-center open-label trial. Six patients (body mass index > 40) will undergo low-frequency VMH-DBS. Data concerning timing, duration, frequency, severity, causal relationships, and associated electrical stimulation patterns regarding side effects or weight changes will be recorded.We expect to demonstrate the safety, identify possible side effects, and to optimize electrophysiological parameters related to VMH-DBS. No clinical or behavioral adverse changes are expected. Weight loss ≥ 3% of the basal weight after 3 mo of electrical stimulation will be considered adequate. Changes in body composition and increase in basal metabolism are expected. The amount of food intake is likely to remain unchanged.The design of this study protocol is to define the safety of the procedure, the surgical parameters important for target localization, and additionally the safety of long-term stimulation of the VMH in morbidly obese patients. Novel neurosurgical approaches to treat metabolic and autonomic diseases can be developed based on the data made available by this investigation.
View details for DOI 10.1093/neuros/nyy024
View details for PubMedID 29538761
The hypothalamus at the crossroads of psychopathology and neurosurgery
2017; 43 (3): E15
The neurosurgical endeavor to treat psychiatric patients may have been part of human history since its beginning. The modern era of psychosurgery can be traced to the heroic attempts of Gottlieb Burckhardt and Egas Moniz to alleviate mental symptoms through the ablation of restricted areas of the frontal lobes in patients with disabling psychiatric illnesses. Thanks to the adaptation of the stereotactic frame to human patients, the ablation of large volumes of brain tissue has been practically abandoned in favor of controlled interventions with discrete targets. Consonant with the role of the hypothalamus in the mediation of the most fundamental approach-avoidance behaviors, some hypothalamic nuclei and regions, in particular, have been selected as targets for the treatment of aggressiveness (posterior hypothalamus), pathological obesity (lateral or ventromedial nuclei), sexual deviations (ventromedial nucleus), and drug dependence (ventromedial nucleus). Some recent improvements in outcomes may have been due to the use of stereotactically guided deep brain stimulation and the change of therapeutic focus from categorical diagnoses (such as schizophrenia) to dimensional symptoms (such as aggressiveness), which are nonspecific in terms of formal diagnosis. However, agreement has never been reached on 2 related issues: 1) the choice of target, based on individual diagnoses; and 2) reliable prediction of outcomes related to individual targets. Despite the lingering controversies on such critical aspects, the experience of the past decades should pave the way for advances in the field. The current failure of pharmacological treatments in a considerable proportion of patients with chronic disabling mental disorders is reminiscent of the state of affairs that prevailed in the years before the early psychosurgical attempts. This article reviews the functional organization of the hypothalamus, the effects of ablation and stimulation of discrete hypothalamic regions, and the stereotactic targets that have most often been used in the treatment of psychopathological and behavioral symptoms; finally, the implications of current and past experience are presented from the perspective of how this fund of knowledge may usefully contribute to the future of hypothalamic psychosurgery.
View details for DOI 10.3171/2017.6.FOCUS17256
View details for Web of Science ID 000410299800009
View details for PubMedID 28859567
- Upholding Scientific Duty Amidst Poisonous Disinformation CUREUS 2020; 12 (7)
Case Report on Deep Brain Stimulation Rescue After Suboptimal MR-Guided Focused Ultrasound Thalamotomy for Essential Tremor: A Tractography-Based Investigation.
Frontiers in human neuroscience
2020; 14: 191
Essential tremor (ET) is the most prevalent movement disorder in adults, and can often be medically refractory, requiring surgical intervention. MRI-guided focused ultrasound (MRgFUS) is a less invasive procedure that uses ultrasonic waves to induce lesions in the ventralis intermedius nucleus (VIM) to treat refractory ET. As with all procedures for treating ET, optimal targeting during MRgFUS is essential for efficacy and durability. Various studies have reported cases of tremor recurrence following MRgFUS and long-term outcome data is limited to 3-4 years. We present a tractography-based investigation on a case of DBS rescue for medically refractory ET that was treated with MRgFUS that was interrupted due to the development of dysarthria during the procedure. After initial improvement, her hand tremor started to recur within 6 months after treatment, and bilateral DBS was performed targeting the VIM 24 months after MRgFUS. DBS induced long-term tremor control with monopolar stimulation. Diffusion MRI tractography was used to reconstruct the dentatorubrothalamic (DRTT) and corticothalmic (CTT) tracts being modulated by the procedures to understand the variability in efficacy between MRgFUS and DBS in treating ET in our patient. By comparing the MRgFUS lesion and DBS volume of activated tissue (VAT), we found that the MRgFUS lesion was located ventromedially to the VAT, and was less than 10% of the size of the VAT. While the lesion encompassed the same proportion of DRTT streamlines, it encompassed fewer CTT streamlines than the VAT. Our findings indicate the need for further investigation of targeting the CTT when using neuromodulatory procedures to treat refractory ET for more permanent tremor relief.
View details for DOI 10.3389/fnhum.2020.00191
View details for PubMedID 32676015
View details for PubMedCentralID PMC7333679
Electrophysiology and Structural Connectivity of the Posterior Hypothalamic Region: Much to Learn From a Rare Indication of Deep Brain Stimulation.
Frontiers in human neuroscience
2020; 14: 164
Cluster headache (CH) is among the most common and debilitating autonomic cephalalgias. We characterize clinical outcomes of deep brain stimulation (DBS) to the posterior hypothalamic region through a novel analysis of the electrophysiological topography and tractography-based structural connectivity. The left posterior hypothalamus was targeted ipsilateral to the refractory CH symptoms. Intraoperatively, field potentials were captured in 1 mm depth increments. Whole-brain probabilistic tractography was conducted to assess the structural connectivity of the estimated volume of activated tissue (VAT) associated with therapeutic response. Stimulation of the posterior hypothalamic region led to the resolution of CH symptoms, and this benefit has persisted for 1.5-years post-surgically. Active contacts were within the posterior hypothalamus and dorsoposterior border of the ventral anterior thalamus (VAp). Delta- (3 Hz) and alpha-band (8 Hz) powers increased and peaked with proximity to the posterior hypothalamus. In the posterior hypothalamus, the delta-band phase was coupled to beta-band amplitude, the latter of which has been shown to increase during CH attacks. Finally, we identified that the VAT encompassing these regions had a high proportion of streamlines of pain processing regions, including the insula, anterior cingulate gyrus, inferior parietal lobe, precentral gyrus, and the brainstem. Our unique case study of posterior hypothalamic region DBS supports durable efficacy and provides a platform using electrophysiological topography and structural connectivity, to improve mechanistic understanding of CH and this promising therapy.
View details for DOI 10.3389/fnhum.2020.00164
View details for PubMedID 32670034
View details for PubMedCentralID PMC7326144
Upholding Scientific Duty Amidst Poisonous Disinformation.
2020; 12 (7): e9339
Because of a recent politically-biased Lancet editorial, the world's opinion has been directed against the Brazilian government over the rising numbers of COVID-19 cases in the country. This is an example of reporting data without accounting for important covariates. Epidemiological figures should always be corrected for population size. In fact, Brazil is not even on the list of the 10 countries with the highest number of deaths per 100,000 people. Belgium, the United Kingdom, and Spain are the most affected countries in this regard. The disinformation presented by a renowned medical journal has ignited severe criticisms against a Chief-of-State for not promoting a generalized lockdown in a country of continental size. As scientists, we have a duty to stress the caveats of science instead of fueling political attacks, and we should refrain from jumping to uninformed conclusions without considering well-analyzed data. Moreover, while there is no evidence to endorse the efficacy of a generalized lockdown in socioeconomically vulnerable populations, it is undoubtedly associated with severe nationwide adverse effects.
View details for DOI 10.7759/cureus.9339
View details for PubMedID 32850213
View details for PubMedCentralID PMC7444859
Pediatric peripheral nerve tumors: clinical and surgical aspects.
Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
Pediatric peripheral nerve tumors (PNTs) are rare. Most are related to neurofibromatosis type 1 (NF1) with the potential for malignancy. An ongoing debate occurs about the best approach to such patients. This study describes a cohort of pediatric patients with PNTs and discusses clinical characteristics and surgical treatment.We retrospectively reviewed the charts of seven pediatric patients with eight PNTs surgically treated from 2007 to 2018. Information concerning patient demographics, clinical presentation, PNTs characteristics, treatment choice, and outcome were recorded.All children presented with intense pain and a palpable mass. Three of the eight tumors were associated with a neurological deficit. Among the four patients with NF1, two had a neurofibroma and two a malignant peripheral nerve sheath tumor (MPNST). Histologically, three of the lesions were a benign peripheral nerve sheath tumor (BPNST), three a MPNST, and one each a desmoid tumor and Ewing's sarcoma. Two of the eight tumors underwent partial tumor excision and six gross total excisions.Intense pain at rest, day, and/or night, preventing normal activities; a palpable, hard, immobile mass; an intense Tinel's sign related to the lump; clinical evidence of NF1; and high-speed growth of a tumor in the trajectory of the nerve or plexus should alert the clinician to the potential for malignancy. Preoperative biopsy is not indicated when clinical and imaging findings suggest a benign tumor. The surgical management of PNTs must be to achieve total resection, including wide margins with malignant tumors, though this is not always possible.
View details for DOI 10.1007/s00381-019-04306-w
View details for PubMedID 31346736
A Neglected Cause of Iatrogenic Brachial Plexus Injuries in Psychiatric Patients
2018; 82 (3): 307–11
Psychiatric patients are often kept immobilized during hospitalization to avoid self-inflicted injuries and danger to third parties. Inadequate positioning can lead to brachial plexus injuries (BPI).To present a series of 5 psychiatric patients with BPI after being left sedated and restrained for prolonged periods of time during hospitalization.We retrospectively reviewed the charts of 5 psychiatric patients with iatrogenic BPI referred by other institutions to our service. The restraint technique adopted by those institutions consisted of a high-thoracic restraint. All patients underwent complete clinical and neurological examination at our center. Information concerning patient demographics, BPI characteristics, treatment choice, and ultimate outcome was recorded.Three patients were male. The age of our patients ranged from 25 to 61 years old (mean: 41.2; median: 43). Three patients had a diagnosis of bipolar disorder while 2 had schizophrenia. Duration of immobilization ranged from 5 to 168 h (mean: 77.8; median: 72). Four patients presented with a unilateral right-sided lesion. Time to presentation ranged from 1 to 9 mo (mean: 4.2; median: 4). All patients also had intense pain and axillary lesions. Four patients received conservative treatment with partial or full functional recovery and complete pain resolution. The remaining patients underwent surgical repair and experienced good functional outcome.Psychiatric patients who need to be sedated and immobilized must be monitored closely, as BPI can occur from high-thoracic restraints. When such an injury occurs, the patient must be referred to a center specialized in peripheral nerve surgery and rehabilitation.
View details for DOI 10.1093/neuros/nyx162
View details for Web of Science ID 000439685800023
View details for PubMedID 28521032
Double Blinded Randomized Trial of Subcutaneous Trigeminal Nerve Stimulation as Adjuvant Treatment for Major Unipolar Depressive Disorder.
More than 30% of major depressive disorder patients fail to respond to adequate trials of medications and psychotherapy. While modern neuromodulation approaches (ie, vagal nerve stimulation, deep brain stimulation) are yet to prove their efficacy for such cases in large randomized controlled trials, trigeminal nerve stimulation (TNS) has emerged as an alternative with promising effects on mood disorders.To assess efficacy, safety, tolerability, and placebo effect duration of continuous subcutaneous TNS (sTNS) in treatment-resistant depression (TRD).The TREND study is a single-center, double-blind, randomized, controlled, phase II clinical trial. Twenty unipolar TRD patients will receive V1 sTNS as adjuvant to medical therapy and randomized to active vs sham stimulation throughout a 24-wk period. An additional 24-wk open-label phase will follow. Data concerning efficacy, placebo response, relapse, and side effects related to surgery or electrical stimulation will be recorded. We will use the HDRS-17, BDI-SR, IDS_SR30, and UKU scales.The main outcome measure is improvement in depression scores using HAM-17 under continuous sTNS as adjuvant to antidepressants. Active stimulation is expected to significantly impact response and remission rates. Minor side effects are expected due to the surgical procedure and electrical stimulation. The open-label phase should further confirm efficacy and tolerability.This study protocol is designed to define efficacy of a novel adjuvant therapy for TRD. We must strive to develop safe, reproducible, predictable, and well-tolerated neuromodulation approaches for TRD patients impaired to manage their lives and contribute with society.
View details for DOI 10.1093/neuros/nyy420
View details for PubMedID 30272245